American Association for Cancer Research
10780432ccr161874-sup-167388_1_supp_3672327_lfz5g6.docx (684.87 kB)

Supplementary Data from FCGR Polymorphisms Influence Response to IL2 in Metastatic Renal Cell Carcinoma

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journal contribution
posted on 2023-03-31, 19:49 authored by Amy K. Erbe, Wei Wang, Jacob Goldberg, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A. Mendonca, Yiqiang Song, Jacquelyn A. Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, James W. Mier, David J. Panka, David F. McDermott, Paul M. Sondel

Supplementary Table 1. Frequency of FCGR genotypes and HWE test. Supplementary Table 2. PFS Clinical Outcome Assessment of FCGR2A, FCGR3A and FCGR2C SNPs. Supplementary Table 3. Clinical Outcome Parameters were Assessed for FCGR3A, FCGR2A and FCGR2C SNPs within the Group of 100 Patients with Clear Cell Histology that were Genotyped.


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National Center for Advancing Translational Sciences

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Purpose: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated antitumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. Prior studies of patients with cancer treated with immunotherapy indicate that FCGR polymorphisms can influence antitumor response for certain immunotherapies that act via therapeutically administered mAbs or via endogenous tumor-reactive antibodies induced from tumor antigen vaccines. The previously published “SELECT” trial of high-dose aldesleukin (HD-IL2) for metastatic renal cell carcinoma resulted in an objective response rate of 25%. We evaluated the patients in this SELECT trial to determine whether higher-affinity FCGR polymorphisms are associated with outcome.Experimental Design: SNPs in FCGR2A, FCGR3A, and FCGR2C were analyzed, individually and in combination, for associations between genotype and clinical outcome.Results: When higher-affinity genotypes for FCGR2A, FCGR3A, and FCGR2C were considered together, they were associated with significantly increased tumor shrinkage and prolonged survival in response to HD-IL2.Conclusions: Although associations of higher-affinity FCGR genotype with clinical outcome have been demonstrated with mAb therapy and with idiotype vaccines, to our knowledge, this is the first study to show associations of FCGR genotypes with outcome following HD-IL2 treatment. We hypothesize that endogenous antitumor antibodies may engage immune cells through their FCGRs, and HD-IL2 may enhance antibody-induced tumor destruction, or antibody-enhanced tumor antigen presentation, via augmented activation of innate or adaptive immune responses; this FCGR-mediated immune activity would be augmented through immunologically favorable FCGRs. Clin Cancer Res; 23(9); 2159–68. ©2016 AACR.